Metabolic Reprogramming in Tumor Radioresistance

In response to ionising radiation, tumour cells undergo profound metabolic reprogramming that underpins their ability to survive and repair damage. Hallmarks of this process include a shift from mitochondrial oxidative phosphorylation towards enhanced glycolysis and lactate production, even in oxygenated conditions – a phenomenon often referred to as the Warburg effect. Simultaneously, hypoxic regions within solid tumours exacerbate adaptive responses that promote DNA repair, redox homeostasis and autophagic clearance, thereby limiting radiotherapy efficacy. Key molecular players encompass glycolytic enzymes, lactate transporters and transcriptional regulators that modulate energy flux and reactive oxygen species generation. Altered mitochondrial function and increased reliance on alternative substrates such as glutamine further contribute to a resistant phenotype. Together, these alterations create a metabolic landscape in which cancer cells can withstand genotoxic stress, evade immune surveillance and regrow after treatment. Understanding these interconnected pathways has global significance, offering avenues for the development of targeted radiosensitising strategies and the optimisation of combination therapies to improve outcomes across diverse tumour types.

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Metabolic Reprogramming in Tumor Radioresistance publication trend

The graph below shows the total number of articles in metabolic reprogramming in tumor radioresistance across all publications each year (not limited to Nature Index journals).

Technical terms

Metabolic reprogramming: The alteration of cellular energy pathways, favouring glycolysis over oxidative phosphorylation in cancer cells.

Radioresistance: The capacity of tumour cells to survive and repair damage induced by ionising radiation.

Warburg effect: The preference of cancer cells for converting glucose into lactate, even in the presence of oxygen.

Hypoxia: A state of reduced oxygen availability within the tumour microenvironment that promotes adaptive stress responses.

Reactive oxygen species (ROS): Highly reactive molecules derived from oxygen that can damage cellular components but also mediate signalling in radiotherapy.

References

1. A Novel Nanozyme to Enhance Radiotherapy Effects by Lactic Acid Scavenging, ROS Generation, and Hypoxia Mitigation. Advanced Science (2024).
2. Feedback loop between hypoxia and energy metabolic reprogramming aggravates the radioresistance of cancer cells. Experimental Hematology & Oncology (2024).
3. TAB182 regulates glycolytic metabolism by controlling LDHA transcription to impact tumor radiosensitivity. Cell Death & Disease (2024).